Mutation of chromosome-protecting gene linked to more aggressive forms of human cancer for first time: study

Mutation of chromosome-protecting gene linked to aggressive cancers

Mutation of an essential gene responsible for protecting the ends of chromosomes (or telomeres) from the fraying and damage of cancerous tumours and aging has been linked to human cancer for the first time.

In a study published this week in the journal Nature Genetics, Carlos López-Otín and other researchers working as part of the Spanish Consortium in the study of the Chronic Lymphocytic Leukaemia Genome say they’ve discovered a “previously unknown route” that tumour cells use to alter telomeres.

Cancer will become a manageable disease rather than a death sentence thanks to a revolutionary treatment which will be available within five years, British specialists predict.

All patients will soon have their tumour’s DNA, its genetic code, sequenced, enabling doctors to ensure they give exactly the right drugs to keep the disease at bay.

Doctors hope it will be an important step towards transforming cancer into a chronic rather than fatal disease.

The technique could enable terminally ill patients, who can currently expect to live only months, to carry on for a decade or more in relatively good health, according to specialists at the Institute of Cancer Research in London.

“Chronic Lymphocytic Leukemia is the most frequent leukemia in Western countries,” López-Otín said. “Once the most frequent genetic changes in its development have been decoded, it’s necessary to discover the biochemical mechanisms altered by those changes, in order to be able to improve the diagnosis and treatment of this disease.”

Following up on work of the last two years, researchers focused on mutations affecting POT1, one of the genes that works to protect the ends of chromosomes, the telomeres.

“We have been studying telomere biology for a long time, given that alterations in telomere maintenance are associated with cancer and aging,” said María Blasco, the director of the Spanish National Cancer Research Centre (CNIO), and another researcher on the study.

This was the first time, however, that a gene with a chromosome end-protecting function was found to have mutated due to cancer.

After analyzing the genome of 341 chronic lymphocytic leukemia patients — comparing for each case the genes from healthy cells with those of tumour cells — researchers discovered POT1 is one of the most frequently mutated genes for the disease. They also noted that, in general, the disease shows a significant amount of genetic diversity, with frequently-repeated mutations (such as the one for POT1) showing up in only 15% of patients.

For the telomere-protecting POT1, however, researchers say they found some interesting characteristics: While only 3.5% of patients with chronic lymphocytic leukemia showed POT1 mutations, the figure rose to 9% in a subgroup of patients suffering from an especially aggressive form of the disease. The study authors say that means that developing therapies that intervene along this gene’s pathway could alter outcomes for the cancer patients suffering with the most virulent strains of the disease.

They go on to note that identifying genes and mutations such as the one affecting POT1 are the first steps towards the goal of “personalized cancer therapies,” which can be adapted to the genetic profile of each individual tumour.